allergy 1 and IV hypersensitivity

Question 1

What is atopy?

Answer 1

genetic predisposition to allergy

Question 2

Do you have allergy symptoms in sensitisation?

Answer 2

nope

Question 3

what two systems does anaphylaxis affect?

Answer 3

circulation (hypotension) and respiration (bronchoconstriction)

Question 4

What is anaphylactoid reactions driven by?

Answer 4

Non-IgE mediated mast cell degranulation.

Question 5

Why kind of Th responses are induced in allergy and what cytokines involved in IgE production?

Answer 5

Th2, cytokines Il4 Il and Il13

Question 6

What factors cause immediate allergic reactions?

Answer 6

contents of granules in mast cells which are released: histamine, TNFa, heparin and proteases.

Question 7

what are mid and late responses to mast cell activation?

Answer 7

leukotrienes, prostaglandins and then cytokine production e.g. IL-4, IL-13 (requires transcription)

Question 8

effects of histamine on blood vessels?

Answer 8

vasodilation and increased vasopermeabiliyt leading to liquid extravasation- swelling- and hypotension (anaphylaxis).

Question 9

effects of histamine on smooth muscles?

Answer 9

Stimulates smooth muscle contraction in bronchi and gut.
Also stimulates mucus secretion in these areas as well as in the nose.
Neural stimulation causes itching and sneezing.

Question 10

effects of late release of leukotrienes and cytokines responsible?

Answer 10

chemotaxis of eosinophils, epithelial damage and shedding.

can cause a biphasic reaction- initiating anaphylactoid reactoins.

Question 11

What can chronic mast cell stimulation and leukotriene and cytokine release lead to?

Answer 11

T cell inflammation, collagen deposition and smooth muscle hypertrophy.

Question 12

What sort of questions are asked when diagnosing allergies?

Answer 12

time since exposure (needs to be less than an hour for immediate reaction)

reproducible?

where do you have symptoms (different antigens)

seasonal or perennial?

food is cooked or raw?

reaciton in exercise (wheat associated exercise dependent anaphylaxis)

Question 13

How long after anaphylaxis would you test for specific IgE levels?

Answer 13

3-4 weeks

Question 14

What are positive and negative controls for skin prick tests?

Answer 14

positive (is nettle antigen/ histamine)

negative control is just saline (just to test for non specific redness).

Question 15

How to treat anaphylaxis?

Answer 15

adrenalin, bronchodilators salbutamol/ oxgyen

antihistmaines/steroids.

Question 16

why would you measure tryptase levels?

Answer 16

released at the same time as histamine, but much longer half life than short histamine half life.

Question 17

Condition where tryptase can remain high even after 24 hrs?

Answer 17

systemic mastocytosis.

Question 18

How does venom immunotherapy work?

Answer 18

weekly small doses which are built up. Moves to every 8 weeks.

induces Treg responses, IL-10 and TGF-B dampen down the Th2 response.

Also generates inert IgG4 antibody production which competes with IgE for the environmental Ag.

Question 19

When may you not give venom immunotherapy?

Answer 19

severe asthma, autoimmune disease, or patients on immunosuppressive or modulatory drugs.
cancer patients and during pregnancy.

Question 20

What else could someone be allergic to if they have allergic rhinitis against birch pollen?

Answer 20

apples (but not cooked form)

Question 21

What progression is often seen from early onset of eczema?

Answer 21

eczema to allergic rhinitis and then asthma.

Question 22

examples of allergens in allergic rhinitis?

Answer 22

pollen, animal dander and dust mite debris.

Question 23

Early and late symptoms of allergic rhinitis?

Answer 23

sneezing, itching, watery eye and itchy chest.

late: congested nose and inflamed and swollen eyes.

Question 24

what cytokines recruit and promote the survival of eosinophils and basophils?

Answer 24

IL3 and Il-5

Question 25

What other Late cytokines in allergic rhinitis?

Answer 25

EPO, ECP, EDN-MBP

Question 26

what cells can be recruited in late stage of allergic rhinitis?

Answer 26

Th2 cells and esoniphils- contribute towards inflammation and congestion.

Question 27

What treatment can inhibit cytokine produciton in allergic rhinitis (late phase response?)

Answer 27

steroid nasal sprays - immunotherapy only for severe cases.

Question 28

Can you eat raw or cooked food in a) oral allergy syndrome?

Answer 28

allergic to raw foods, with common antigens in to pollen e.g. birch pollen and apple.

Question 29

Common Antigens in pollen and food in oral allergy sydnrome?

Answer 29

PR-10 protein and profilins.

Question 30

Antigens in pollen and food causing systemic reactions? Which isn't safe to eat when cooked?

Answer 30

lipid transfer proteins and storage proteins. Storage proteins are resistant to changes when cooking- unsafe to eat cooked food as well as raw food (includes a lot of nuts)

Question 31

What are some examples of delayed sensitivity?

Answer 31

atopic dermatitis and contact dermatitis.

Question 32

What sorts of defects contribute to atopic dermatitis?

Answer 32

barrier skin dysfunctions e.g. fillagrin, increased epidermal water loss and decreased ceramides.

Question 33

Pathogenesis of atopic dermatitis?

Answer 33

Barrier defects may mean antigen uptake is increased, Taken up by LCs and DCs triggering a Th2 response. Contact with allergen causes allergic reaction and itchiness, scratching then causes damanage and cytokine release and a Th1/ Th17 response. eosinophils and macrophages also implicated in chronic response.

Question 34

What cytokines can drive Th2 response in atopic dermatitis?

Answer 34

IL-4 Il-10 TSLP

Question 35

how is NFAT triggered and what can prevent this?

Answer 35

ca2+ influx in T cell activation leads to calmodulin binding and activation of calcineurin. Calcineurin will dephosphorylate NFAT- NFAT translocation. tacrolimus will bind to FKBP to prevent calcineurin activation.

Question 36

what does dupilumab inhibit and what condition?

Answer 36

inhibits IL-4, IL-13 ni atopic dermatitis to imporve pruritus.

Question 37

What test is done for contact dermatitis?

Answer 37

patch test- affixed to back for 48-72 hours.

Question 38

What can allergens do that cause contact dermatitis?

Answer 38

lipophilic and can cross epidermis, can haptenate proteins e.g. albumin.

Question 39

Mechanism of contact dermatitis sensitisation

Answer 39

lipophilic antigen adsorbed across epidermis, binds to host protein e,.g albumin to create a neoepitope that can be taken up by LCs. Activation of e.g TLR4 by Ni or other danger signals triggered by hapten. uptake and presentation of hapten on cell surface. Also primes CD8 response ( which can have keratinocyte cytotoxicity).

Question 40

What can be a non -IgE mediated response?

Answer 40

Asthma and contact dermatitis.

Question 41

Genetic factors for allergy?

Answer 41

filaggrin (in keratinocytes- nnull mutations Atopic dermatitis) ADAM 33 metalloprotease has a role in asthma. IL-4 Il13 MHC FcER1.